Cargando…

Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control

The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and prog...

Descripción completa

Detalles Bibliográficos
Autores principales: Ranasinghe, Srinika, Cutler, Sam, Davis, Isaiah, Lu, Richard, Soghoian, Damien Z., Qi, Ying, Sidney, John, Kranias, Gregory, Flanders, Michael, Lindqvist, Madelene, Kuhl, Bjorn, Alter, Galit, Deeks, Steven G., Walker, Bruce D., Gao, Xiaojiang, Sette, Alessandro, Carrington, Mary, Streeck, Hendrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974408/
https://www.ncbi.nlm.nih.gov/pubmed/23793098
http://dx.doi.org/10.1038/nm.3229
_version_ 1782479462962561024
author Ranasinghe, Srinika
Cutler, Sam
Davis, Isaiah
Lu, Richard
Soghoian, Damien Z.
Qi, Ying
Sidney, John
Kranias, Gregory
Flanders, Michael
Lindqvist, Madelene
Kuhl, Bjorn
Alter, Galit
Deeks, Steven G.
Walker, Bruce D.
Gao, Xiaojiang
Sette, Alessandro
Carrington, Mary
Streeck, Hendrik
author_facet Ranasinghe, Srinika
Cutler, Sam
Davis, Isaiah
Lu, Richard
Soghoian, Damien Z.
Qi, Ying
Sidney, John
Kranias, Gregory
Flanders, Michael
Lindqvist, Madelene
Kuhl, Bjorn
Alter, Galit
Deeks, Steven G.
Walker, Bruce D.
Gao, Xiaojiang
Sette, Alessandro
Carrington, Mary
Streeck, Hendrik
author_sort Ranasinghe, Srinika
collection PubMed
description The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4(+) T cell responses to Gag and Nef.
format Online
Article
Text
id pubmed-3974408
institution National Center for Biotechnology Information
language English
publishDate 2013
record_format MEDLINE/PubMed
spelling pubmed-39744082014-04-03 Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control Ranasinghe, Srinika Cutler, Sam Davis, Isaiah Lu, Richard Soghoian, Damien Z. Qi, Ying Sidney, John Kranias, Gregory Flanders, Michael Lindqvist, Madelene Kuhl, Bjorn Alter, Galit Deeks, Steven G. Walker, Bruce D. Gao, Xiaojiang Sette, Alessandro Carrington, Mary Streeck, Hendrik Nat Med Article The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4(+) T cell responses to Gag and Nef. 2013-06-23 2013-07 /pmc/articles/PMC3974408/ /pubmed/23793098 http://dx.doi.org/10.1038/nm.3229 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ranasinghe, Srinika
Cutler, Sam
Davis, Isaiah
Lu, Richard
Soghoian, Damien Z.
Qi, Ying
Sidney, John
Kranias, Gregory
Flanders, Michael
Lindqvist, Madelene
Kuhl, Bjorn
Alter, Galit
Deeks, Steven G.
Walker, Bruce D.
Gao, Xiaojiang
Sette, Alessandro
Carrington, Mary
Streeck, Hendrik
Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title_full Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title_fullStr Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title_full_unstemmed Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title_short Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
title_sort association of hla-drb1-restricted cd4(+) t cell responses with hiv immune control
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974408/
https://www.ncbi.nlm.nih.gov/pubmed/23793098
http://dx.doi.org/10.1038/nm.3229
work_keys_str_mv AT ranasinghesrinika associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT cutlersam associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT davisisaiah associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT lurichard associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT soghoiandamienz associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT qiying associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT sidneyjohn associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT kraniasgregory associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT flandersmichael associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT lindqvistmadelene associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT kuhlbjorn associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT altergalit associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT deekssteveng associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT walkerbruced associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT gaoxiaojiang associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT settealessandro associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT carringtonmary associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol
AT streeckhendrik associationofhladrb1restrictedcd4tcellresponseswithhivimmunecontrol